Bupisen

Package leaflet: Information for the user

BUPISEN 2.5 mg/ml injectable solution, 5 mg/ml injectable solution, hyperbaric 5 mg/ml injectable solution, hyperbaric 7.5 mg/ml injectable solution, hyperbaric 10 mg/ml injectable solution

Bupivacaine hydrochloride
Equivalent medicine
Please read all of this leaflet carefully before you use this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What BUPISEN is and what it is used for
2. What you need to know before using BUPISEN
3. How to use BUPISEN
4. Possible side effects
5. How to store BUPISEN
6. Contents of the pack and other information

1. What BUPISEN is and what it is used for

BUPISEN contains the active substance bupivacaine hydrochloride and belongs to a group of medicines called local anaesthetics, which are used prior to surgical procedures to induce anaesthesia.
BUPISEN can be used to induce peripheral anaesthesia (local infiltration, nerve block, locoregional anaesthesia, sympathetic block, sacral epidural, spinal -subarachnoid-).
BUPISEN is indicated, either alone or in combination with other narcotic medicines, for procedures in:

• general surgery;
• bones and joints (orthopaedics);
• eyes (ophthalmology);
• ear, nose and throat (otorhinolaryngology);
• oral cavity (dentistry);
• genital area and during childbirth (obstetrics-gynaecology);
• skin (dermatology).

2. What you should know before being administered BUPISEN

Do not be administered BUPISEN if:

• you are allergic to bupivacaine hydrochloride, to similar substances (amide-type local anesthetics), or to any of the other ingredients of this medicine (listed in section 6);
• you are due to undergo regional intravenous anesthesia (Bier Block);
• you suffer from diseases of the central nervous system (meningitis, tumors, poliomyelitis, intracranial hemorrhage), spinal diseases (spondylitis, tuberculosis, tumor), or have recently experienced trauma (fractures);
• you have bacterial infection in the bloodstream (septicemia);
• you have vitamin B12 deficiency (pernicious anemia), associated with spinal cord problems (subacute combined degeneration of the spinal cord);
• you have a bacterial skin infection (pyogenic) at or near the injection site;
• you have experienced heart failure (cardiogenic shock) or have reduced blood volume due to hemorrhage or fluid loss (hypovolemic shock);
• you have coagulation disorders or are taking medications used to prevent blood clotting (anticoagulants).

BUPISEN hyperbaric 7.5 mg/ml solution for injection must not be used for epidural anesthesia during childbirth (obstetric epidural anesthesia).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before being administered BUPISEN.
For epidural anesthesia or peripheral nerve blocks, this medicine must be administered under direct medical supervision, as serious adverse effects may occur, such as:

• cardiac arrest and death; these effects may occur especially when using BUPISEN hyperbaric 7.5 mg/ml solution for injection.

Additionally, during treatment with BUPISEN, central nervous system, heart, and vascular problems (cardiovascular issues, ventricular arrhythmias, ventricular fibrillation, sudden cardiovascular collapse), and death may occur when this medicine is present in high concentrations in the blood—particularly if accidentally injected into a blood vessel (intravascular) or into highly vascularized areas. When BUPISEN is used at recommended doses, blood levels of the medicine do not reach high concentrations.
Serious adverse reactions, including death, have been reported with similar medicines (local anesthetics). Therefore, this medicine will only be administered under strict medical supervision by trained personnel in facilities equipped with emergency measures necessary for urgent treatment.
This medicine must be administered with great caution and under close medical supervision if:

• you are elderly or debilitated;
• you have heart problems (partial or complete heart block), as this medicine may reduce heart contractility (cardiac conduction);
• you have advanced liver disease or severely impaired kidney function;
• you are in the late stages of pregnancy;
• you have reduced blood volume (hypovolemia), as this medicine during intrathecal anesthesia may cause a severe and sudden drop in blood pressure (hypotension);
• you are taking medicines used for heart rhythm disorders (class III antiarrhythmics), such as amiodarone. In this case, your doctor may decide to monitor heart function (electrocardiogram);
• you suffer from nervous system disorders (multiple sclerosis, hemiplegia, paraplegia) or neuromuscular disorders;
• you have sustained major joint trauma or undergone joint surgery, and BUPISEN is to be administered intra-articularly;
• you have reduced cardiovascular function and BUPISEN is to be administered epidurally;
• you are taking medicines used to treat mood disorders (MAOIs, tricyclic antidepressants);
• you are scheduled to undergo an anesthesia procedure called stellate ganglion block.

Your doctor will monitor you during treatment with this medicine, as certain anesthetic techniques may cause adverse effects, including severe ones:

• epidural anesthesia or central nerve block – cardiovascular depression (reduced heart and vascular function) may occur, especially if hypovolemia is already present. Additionally, low blood pressure (hypotension) and slow heart rate (bradycardia) may occur. Hypotension may require immediate intravenous administration of drugs that stimulate the heart (sympathomimetics);

• stellate ganglion block – may cause adverse effects similar to central nerve block, as well as cardiac toxicity with increased or decreased heart rate up to cardiac arrest;

• retrobulbar eye injections – very rarely, temporary loss of vision (transient blindness), cardiovascular collapse (cardiac and circulatory arrest), breathing difficulties (apnea), and seizures may occur, which must be treated immediately;

• retrobulbar or peribulbar eye injections – long-lasting eye muscle disorders may occur; therefore, the lowest doses and concentrations of anesthetic should be used;

• paracervical block – reduced or increased fetal heart rate (bradycardia/tachycardia) may occur. Therefore, fetal heart rate must be monitored during use of this medicine;

• spinal anesthesia – total or high spinal block may occur, leading to cardiovascular depression (impaired heart and circulation) and respiratory depression (impaired breathing). These effects are more likely if you are elderly or in late pregnancy; in such cases, the dose should be reduced;

• intrathecal anesthesia – rare cases of brain damage (paresthesia, anesthesia, motor weakness, and paralysis) have been reported, which in some cases may be permanent;

For local anesthesia in areas such as fingers or the base of the penis, bupivacaine without adrenaline will be administered to prevent tissue damage (ischemic necrosis).
Before administration, your doctor must assess your blood circulation status.
Your doctor may decide to use a test dose of this medicine containing adrenaline to avoid accidental intravenous or intrathecal injection.
During administration, your doctor will closely monitor you and immediately stop treatment at the first sign of alarm, such as altered sensation or drowsiness (altered sensorium).
Rare cases of severe reactions, even in non-allergic individuals, have been reported; therefore, immediate availability of emergency equipment, medications, and trained personnel is required during use of this medicine.

Children
The safety and efficacy of Bupisen in children under 1 year of age have not been established. Only limited data are available.
For epidural anesthesia, the dose must be adjusted according to weight and age.

Other medicines and BUPISEN
Inform your doctor, pharmacist, or nurse if you are currently taking, have recently taken, or might take any other medicines.
Use this medicine with caution and inform your doctor if you are taking:

• other medicines used to reduce pain during surgery (amide-type local anesthetics, such as lidocaine);
• medicines similar to BUPISEN, such as certain medicines used to treat heart rhythm disorders (mexiletine, tocainide);
• medicines used to treat depression (MAOIs, tricyclic antidepressants).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
If you are in the late stage of pregnancy, the dose for spinal anesthesia should be reduced.
Paracervical anesthesia is associated with an increased risk of adverse effects on the fetus (see Warnings and precautions).

Breastfeeding
Use this medicine with caution if breastfeeding, as BUPISEN passes into breast milk in small amounts.

Driving and using machines
BUPISEN may impair your ability to drive or operate machinery.
BUPISEN may cause mild disturbances in mental function and motor control (coordination). If you experience these symptoms, avoid driving or operating machinery.

BUPISEN 2.5 mg/ml and 5 mg/ml solution for injection contains sodium
This medicine contains 3.15 mg/ml (0.137 mmol/ml) of sodium. This should be taken into account in patients with impaired renal function or those on a low-sodium diet.

3. How to use BUPISEN

This medicine will be administered to you by a doctor or trained medical personnel during surgical procedures. If you have any doubts, consult your doctor, pharmacist, or nurse.
The dose and method of administration will be determined by the doctor according to your needs and age.
Vials and syringes do not contain preservatives and are intended for single use only; any unused medicine must be discarded.

Use in adults and children over 12 years of age
The dose should be the lowest possible that ensures adequate anaesthesia. The recommended dose ranges from 2–3 mg to 100–150 mg.
Do not exceed the maximum dose of 150 mg, corresponding to 30 ml of the 5 mg/ml solution and 60 ml of the 2.5 mg/ml solution.

Use in children from 1 to 12 years of age
The doctor will adjust the dose according to body weight.

If you use more BUPISEN than you should
Accidental intravascular injection may cause toxic effects within a few seconds or minutes.
Following administration of an excessive dose of this medicine, toxic effects (systemic toxic reactions) may occur 15–60 minutes after injection.
It is unlikely that BUPISEN hyperbaric, when administered under the recommended conditions, would cause general toxicity. However, if other medicines similar to BUPISEN hyperbaric are administered simultaneously, toxic effects may be additive.
In case of accidental overdose or ingestion, contact your doctor immediately or go to the nearest hospital emergency department.

If you forget to use BUPISEN
This medicine will be administered by a doctor or nurse, so it is unlikely that a dose will be forgotten.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:

Very common (may affect more than 1 in 10 people):

• decrease in blood pressure (hypotension);
• nausea.

Common (may affect up to 1 in 10 people):

• sensory disturbances in legs, arms or other parts of the body (paraesthesiae), dizziness, headache (after puncture in the dura mater, post-dural puncture headache);
• reduced heart rate (bradycardia);
• increase in blood pressure (hypertension);
• vomiting;
• inability of the bladder to empty (urinary retention), involuntary loss of urine (urinary incontinence).

Uncommon (may affect up to 1 in 100 people):

• central nervous system toxicity: seizures, disturbances of sensation around the mouth (circumoral paraesthesia), tongue numbness, intolerance to sounds (hyperacusis), visual disturbances, loss of consciousness, tremor, sensation of emptiness in the head, perception of ringing in the ear (tinnitus), speech disturbances (dysarthria), disturbances in contraction of one or more muscles (paresis), disturbance of sensation (dysaesthesia);
• muscle weakness, back pain.

Rare (may affect up to 1 in 1,000 people):

• allergic reactions, severe allergic reaction (anaphylactic shock);
• nerve inflammation (neuropathy), nerve injury (peripheral nerve injury), inflammation of the membrane covering the brain and spinal cord (arachnoiditis), loss of ability to contract one or more muscles (paresis), movement and sensory disturbances in the lower limbs (paraplegia), total spinal block (unintentional), decrease or loss of contraction in one or more muscles (paralysis);
• double vision (diplopia);
• heart block (cardiac arrest), changes in heart rhythm (cardiac arrhythmias);
• breathing problems (respiratory depression).

Not known (frequency cannot be estimated from the available data):

• excitation, disorientation, dilation of the pupil (mydriasis), increased metabolism and body temperature, contraction of the muscles of mastication (trismus), sweating, increased respiratory rate (tachypnea), bronchial dilation (bronchodilation), increase in blood vessel volume (vasodilation);
• allergic reactions with local manifestations such as skin irritations (urticaria, pruritus) or systemic manifestations such as contraction of bronchial muscles (bronchospasm).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store BUPISEN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What BUPISEN 2.5 mg/ml injectable solution contains

• The active substance is bupivacaine hydrochloride: 1 ml of solution contains 2.5 mg of bupivacaine hydrochloride.
• The other components are: sodium chloride, water for injections.

What BUPISEN 5 mg/ml injectable solution contains

• The active substance is bupivacaine hydrochloride: 1 ml of solution contains 5 mg of bupivacaine hydrochloride.
• The other components are: sodium chloride, water for injections.

What BUPISEN hyperbaric 5 mg/ml injectable solution contains

• The active substance is bupivacaine hydrochloride: 4 ml of solution contain 20 mg of bupivacaine hydrochloride.
• The other components are: glucose, water for injections.

What BUPISEN hyperbaric 7.5 mg/ml injectable solution contains

• The active substance is bupivacaine hydrochloride: 3 ml of solution contain 22.5 mg of bupivacaine hydrochloride.
• The other components are: glucose, water for injections.

What BUPISEN hyperbaric 10 mg/ml injectable solution contains

• The active substance is bupivacaine hydrochloride: 2 ml of solution contain 20 mg of bupivacaine hydrochloride.
• The other components are: glucose, water for injections.

Description of the appearance of BUPISEN and contents of the pack
BUPISEN 2.5 mg/ml and 5 mg/ml injectable solution:
Box containing 10 vials of 1 ml, 2 ml, 5 ml, 10 ml.
Box containing 5 vials of 20 ml.
Pack containing 1 pre-filled single-use syringe of 5 ml and 10 ml.
BUPISEN hyperbaric 5 mg/ml injectable solution:
Sterile pack containing 1 vial of 4 ml.
BUPISEN hyperbaric 7.5 mg/ml injectable solution:
Sterile pack containing 1 vial of 3 ml.
BUPISEN hyperbaric 10 mg/ml injectable solution:
Sterile pack containing 1 vial of 2 ml.

Marketing Authorization Holder and Manufacturer
Industria Farmaceutica Galenica Senese - Via Cassia Nord 351 - Monteroni d’Arbia (SI)

The following information is intended exclusively for doctors or healthcare professionals

Special warnings and precautions for use
Adults and children over 12 years of age
Dosage and method of administration
BUPISEN is usually used in minimal dosages, varying according to the indication, from 2–3 mg to 100–150 mg,
as indicated in the following table for guidance:

Warning: Since the vials and syringes do not contain antimicrobial preservatives, they should be used for a single
administration only. Any unused residue must be discarded.
The maximum dose for an adult and for a single administration should not exceed 150 mg,
corresponding to 30 ml of the 5 mg/ml solution and to 60 ml of the 2.5 mg/ml solution. More generally, the
recommended safe dose not to be exceeded, both in adults and children, is 2 mg/kg for a single
administration.
In prolonged analgesic therapy, doses usually range from 0.25 to 1 mg/kg body weight;
administration may be repeated 2–3 times within 24 hours.
Note: When performing prolonged blocks by repeated bolus injections, the risk of achieving toxic plasma concentrations or inducing local neurotoxicity must be considered.
The dose to be administered should be calculated based on the physician’s experience and knowledge of the patient’s clinical condition. It is necessary to use the lowest doses capable of providing adequate anesthesia. Individual variations may occur with regard to onset time and duration of effect. The extent of anesthetic spread may be difficult to predict but is influenced by the volume of drug administered, especially for isobaric solutions.
To prevent accidental intravascular injection, aspiration should be performed before and during administration of the main dose, which must be injected slowly or in incremental doses. During the procedure, monitor the patient’s vital functions carefully and maintain verbal contact.
When epidural anesthesia is required, it is recommended to precede it with a test dose of 3–5 ml of bupivacaine with adrenaline. Accidental intravascular injection may be recognized by a transient increase in heart rate; accidental intrathecal injection may be recognized by signs of spinal block. At the first sign of toxicity, administration must be stopped immediately.
The specific gravity of Bupisen 2.5 mg/ml and 5 mg/ml is 1.006 at 20°C and 0.997 at 37°C.
Any overdose of local anesthetic must be avoided, and two maximum doses should never be administered without an interval of at least 24 hours.
In any case, the lowest effective doses and concentrations should be used to achieve the desired effect.
BUPISEN 5 mg/ml hyperbaric injectable solution
Neonates, infants, and children above 40 kg
BUPISEN 5 mg/ml hyperbaric solution may be used in children. One of the differences between young children
and adults is the relatively large volume of cerebrospinal fluid (CSF) in infants and neonates, which
requires a relatively higher dose per kg to achieve the same level of block compared to adults.
Pediatric regional anesthesia procedures must be performed by qualified physicians familiar with this
patient population and the technique.
The doses in the table should be considered as guidelines for pediatric use. Individual variations may occur.
Standard reference texts should be consulted regarding factors influencing specific blocking techniques
and individual patient requirements.
The lowest dose necessary to achieve adequate anesthesia should be used.
Recommended dose in neonates, infants, and children

For further information, refer to the Summary of Product Characteristics.